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Depression and Anxiety in Stroke-Related and Alzheimer Disease-Related Pseudobulbar Affect: A TriNetX Retrospective Cohort Study
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Depression and Anxiety in Stroke-Related and Alzheimer Disease-Related Pseudobulbar Affect: A TriNetX Retrospective Cohort Study

Kypros J Dereschuk, Cameron C Asay and Eduardo D Espiridion
Alzheimer disease and associated disorders, Forthcoming
15 May 2026
DOI: https://doi.org/10.1097/WAD.0000000000000727
PMID: 42138134
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Abstract

anxiety depression Alzheimer disease pseudobulbar affect Stroke
Pseudobulbar affect (PBA) is a disorder of emotional expression associated with neurological diseases, including stroke and Alzheimer disease. Depression and anxiety frequently co-occur, but whether psychiatric outcomes differ by neurological etiology remains unclear. To compare the risk and timing of depressive episodes and anxiety disorders in stroke-associated versus Alzheimer disease-associated PBA. We conducted a retrospective cohort study using the TriNetX Global Health Research Network (2020 to 2025). Two mutually exclusive cohorts were identified: PBA with stroke and PBA with Alzheimer disease. Outcomes were depressive episode (ICD-10-CM F32) and anxiety disorder, unspecified (ICD-10-CM F41.9), occurring after PBA diagnosis. One-to-one propensity score matching was performed for age, sex, race, and ethnicity. Kaplan-Meier analyses and Cox proportional hazards models assessed risk and timing. After matching, 1074 patients per cohort were included for depression analysis. Depression occurred in 68.7% of Alzheimer disease-PBA versus 34.7% of stroke-PBA (absolute risk difference 34.0%, P<0.001; HR=2.52, 95% CI: 2.22-2.86). For anxiety (n=946 per cohort), rates were 48.8% versus 24.9% (absolute risk difference 23.9%, P<0.001; HR=1.98, 95% CI: 1.70-2.30). Alzheimer disease-associated PBA confers a higher and earlier risk of depression and anxiety, supporting enhanced psychiatric screening in neurodegenerative disease.

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